rs2069422
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004936.4(CDKN2B):c.156+771C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,216 control chromosomes in the GnomAD database, including 62,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.91 ( 62721 hom., cov: 32)
Consequence
CDKN2B
NM_004936.4 intron
NM_004936.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.493
Genes affected
CDKN2B (HGNC:1788): (cyclin dependent kinase inhibitor 2B) This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]
CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2B | NM_004936.4 | c.156+771C>A | intron_variant | ENST00000276925.7 | |||
CDKN2B-AS1 | NR_003529.3 | n.371+12866G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2B | ENST00000276925.7 | c.156+771C>A | intron_variant | 1 | NM_004936.4 | P1 | |||
CDKN2B-AS1 | ENST00000650946.1 | n.29+12866G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.908 AC: 138078AN: 152098Hom.: 62682 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.908 AC: 138174AN: 152216Hom.: 62721 Cov.: 32 AF XY: 0.909 AC XY: 67693AN XY: 74434
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3458
ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at